Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

5-Fluorouracil-Impregnated PLGA Coated Gold Nanoparticles for Augmented Delivery to Lung Cancer: In Vitro Investigations

Author(s): Rashmi Gupta, Leena Vishwakarma, Sunil Kant Guleri and Gourav Kumar*

Volume 22, Issue 12, 2022

Published on: 07 March, 2022

Page: [2292 - 2302] Pages: 11

DOI: 10.2174/1871520622666211224103110

Price: $65

conference banner
Abstract

Background: The study aimed to investigate the augmented cytotoxic effects of polymer-coated (polylactic- co-glycolic acid-PLGA) gold nanoparticles (GNPs) carrying 5-fluorouracil (5-FU) in the management of lung cancer.

Methods: In this study, several formulations were prepared using a double emulsion (water-oil-water) method and evaluated for drug release behavior, compatibility, cell line toxicity (A549), and apoptosis assessment.

Results: Characterization results showed spherical polydispersed particles with size 29.11-178.21 nm, polydispersity index (PDI) 0.191-292, and zeta potential (ZP) 11.19-29.21 (-mV), respectively. Compared to others, the optimized polymer-coated 5-FU loaded gold nanoparticles (PFGNPs) illustrated a maximum drug loading (93.09±10.75%). The percent cumulative drug release of polymer-coated 5-FU loaded nanoparticles (PFNPs), 5-FU loaded gold nanoparticles (FGNPs), (PFGNPs) and 5-FU solution were 47.87±1.5, 41.09±1.8, 56.31±1.05, and 98.8±4.2%, respectively, over 10 h. following zero-order release kinetics (except 5-FU solution). From the MTT results, the cytotoxic effect of PFGNPs on the A549 cells was 82.89% compared to the 5-FU solution (74.91 %). EGFR and KRAS gene expression analysis under the influence of PFNPs, FGNPs, PFGNPs, and 5-FU was studied and observed maximum potency for PFNPs.

Conclusion: PLGA coated biogenic gold nanoparticles have a combined effect to achieve high drug loading, sustained delivery, improved efficacy, and enhanced permeation. Conclusively, the approach may be promising to control lung cancer with reduced toxicity and improved efficacy.

Keywords: Biogenic gold nanoparticles, 5-fluorouracil, polymer-coated, A549 lung cancer cell lines, apoptosis assessment, drug delivery.

« Previous Next »
Graphical Abstract

[1]
Torre, L.A.; Siegel, R.L.; Jemal, A. Lung cancer statistics. Adv. Exp. Med. Biol., 2016, 893, 1-9.
[http://dx.doi.org/10.1007/978-3-319-24223-1_1] [PMID: 26667336]
[2]
Hayashi, H.; Kurata, T.; Nakagawa, K. Gemcitabine: Efficacy in the treatment of advanced stage nonsquamous non-small cell lung cancer. Clin. Med. Insights Oncol., 2011, 5, 177-184.
[http://dx.doi.org/10.4137/CMO.S6252] [PMID: 21695043]
[3]
Daga, A.; Ansari, A.; Patel, S.; Mirza, S.; Rawal, R.; Umrania, V. Current drugs and drug targets in non-small cell lung cancer: limitations and opportunities. Asian Pac. J. Cancer Prev., 2015, 16(10), 4147-4156.
[http://dx.doi.org/10.7314/APJCP.2015.16.10.4147] [PMID: 26028064]
[4]
Guo, T.; Holzberg, T.R.; Lim, C.G.; Gao, F.; Gargava, A.; Trachtenberg, J.E.; Mikos, A.G.; Fisher, J.P. 3D printing PLGA: A quantitative examination of the effects of polymer composition and printing parameters on print resolution. Biofabrication, 2017, 9(2), 024101.
[http://dx.doi.org/10.1088/1758-5090/aa6370] [PMID: 28244880]
[5]
Huang, C.Y.; Ju, D.T.; Chang, C.F.; Muralidhar Reddy, P.; Velmurugan, B.K. A review on the effects of current chemotherapy drugs and natural agents in treating non-small cell lung cancer. Biomedicine (Taipei), 2017, 7(4), 23.
[http://dx.doi.org/10.1051/bmdcn/2017070423] [PMID: 29130448]
[6]
Lee, J.J.; Beumer, J.H.; Chu, E. Therapeutic drug monitoring of 5-fluorouracil. Cancer Chemother. Pharmacol., 2016, 78(3), 447-464.
[http://dx.doi.org/10.1007/s00280-016-3054-2] [PMID: 27217046]
[7]
Chaudhary, S.; Umar, A.; Mehta, S.K. Surface functionalized selenium nanoparticles for biomedical applications. J. Biomed. Nanotechnol., 2014, 10(10), 3004-3042.
[http://dx.doi.org/10.1166/jbn.2014.1985] [PMID: 25992427]
[8]
Liu, W.; Li, X.; Wong, Y.S.; Zheng, W.; Zhang, Y.; Cao, W.; Chen, T. Selenium nanoparticles as a carrier of 5-fluorouracil to achieve anticancer synergism. ACS Nano, 2012, 6(8), 6578-6591.
[http://dx.doi.org/10.1021/nn202452c] [PMID: 22823110]
[9]
Ohya, Y.; Takei, T.; Kobayashi, H.; Ouchi, T. Release behaviour of 5-fluorouracil from chitosan-gel microspheres immobilizing 5-fluorouracil derivative coated with polysaccharides and their cell specific recognition. J. Microencapsul., 1993, 10(1), 1-9.
[http://dx.doi.org/10.3109/02652049309015307] [PMID: 8383199]
[10]
Wen, H.; Jung, H.; Li, X. Drug delivery approaches in addressing clinical pharmacology-related issues: opportunities and challenges. AAPS J., 2015, 17(6), 1327-1340.
[http://dx.doi.org/10.1208/s12248-015-9814-9] [PMID: 26276218]
[11]
Han, J.; Zhao, D.; Li, D.; Wang, X.; Jin, Z.; Zhao, K. Polymer-based nanomaterials and applications for vaccines and drugs. Polymers (Basel), 2018, 10(1), 1-14.
[http://dx.doi.org/10.3390/polym10010031] [PMID: 30966075]
[12]
Martins, C.; Sousa, F.; Araújo, F.; Sarmento, B. Functionalizing PLGA and PLGA derivatives for drug delivery and tissue regeneration applications. Adv. Healthc. Mater., 2018, 7(1), 1701035.
[http://dx.doi.org/10.1002/adhm.201701035] [PMID: 29171928]
[13]
Mu, L.; Feng, S.S. A novel controlled release formulation for the anticancer drug paclitaxel (Taxol): PLGA nanoparticles containing vitamin E TPGS. J. Control. Release, 2003, 86(1), 33-48.
[http://dx.doi.org/10.1016/S0168-3659(02)00320-6] [PMID: 12490371]
[14]
Leelakanok, N.; Geary, S.; Salem, A. Fabrication and use of poly (d, l-lactide-co-glycolide)-based formulations designed for modified release of 5-fluorouracil. J. Pharm. Sci., 2018, 107(2), 513-528.
[http://dx.doi.org/10.1016/j.xphs.2017.10.012] [PMID: 29045885]
[15]
Leelakanok, N.; Geary, S.M.; Salem, A.K. Antitumor efficacy and toxicity of 5-fluorouracil-loaded poly (lactide co-glycolide) pellets. J. Pharm. Sci., 2018, 107(2), 690-697.
[http://dx.doi.org/10.1016/j.xphs.2017.10.005] [PMID: 29031952]
[16]
Boisselier, E.; Astruc, D. Gold nanoparticles in nanomedicine: Preparations, imaging, diagnostics, therapies and toxicity. Chem. Soc. Rev., 2009, 38(6), 1759-1782.
[http://dx.doi.org/10.1039/b806051g] [PMID: 19587967]
[17]
Gupta, P.; Balaji, R.; Parani, M.; Chandra, T.S.; Shukla, P.; Kumar, A.; Bandopadhyay, R. Phylogenetic analysis and biological characteristic tests of marine bacteria isolated from Southern ocean (Indian sector) water. Acta Oceanol. Sin., 2015, 34(8), 73-82.
[http://dx.doi.org/10.1007/s13131-015-0709-5]
[18]
Gupta, R.; Padmanabhan, P. Biogenic synthesis and characterization of gold nanoparticles by novel marine bacteria Marinobacter Algicola: Progression from nanospheres to various geometrical shapes. J. Microbiol. Biotechnol. Food Sci., 2018, 8(1), 732-737.
[http://dx.doi.org/10.15414/jmbfs.2018.8.1.732-737]
[19]
Gupta, R.; Kumar, G.; Das, S.S.; Alkahtani, S.; Alkahtane, A.; Aldahmash, B.; Alarifi, S.; Almutairi, B.; Albasher, G.; Nayak, A.K.; Hasnain, M.S. Crystal growth and kinetic behaviour of Pseudoalteromonas espejiana assisted biosynthesized gold nanoparticles. Oxid. Med. Cell. Longev., 2020, 2020, 6501294.
[http://dx.doi.org/10.1155/2020/6501294] [PMID: 32774681]
[20]
Sharma, N.; Pinnaka, A.K.; Raje, M.; Fnu, A.; Bhattacharyya, M.S.; Choudhury, A.R. Exploitation of marine bacteria for production of gold nanoparticles. Microb. Cell Fact., 2012, 11(1), 86.
[http://dx.doi.org/10.1186/1475-2859-11-86] [PMID: 22715848]
[21]
Zhang, Z.; Wang, X.; Li, B.; Hou, Y.; Yang, J.; Yi, L. Development of a novel morphological paclitaxel-loaded PLGA microspheres for effective cancer therapy: In vitro and in vivo evaluations. Drug Deliv., 2018, 25(1), 166-177.
[http://dx.doi.org/10.1080/10717544.2017.1422296] [PMID: 29299936]
[22]
Kumar, G.; Ghosh, M.; Pandey, D.M. Method development for optimised green synthesis of gold nanoparticles from Millettia pinnata and their activity in non-small cell lung cancer cell lines. IET Nanobiotechnol., 2019, 13(6), 626-633.
[http://dx.doi.org/10.1049/iet-nbt.2018.5410] [PMID: 31432797]
[23]
Nirmal, G.R.; Lin, Z.C.; Tsai, M.J.; Yang, S.C.; Alalaiwe, A.; Fang, J.Y. Photothermal treatment by PLGA-gold nanorod-isatin nanocomplexes under near-infrared irradiation for alleviating psoriasiform hyperproliferation. J. Control. Release, 2021, 333(333), 487-499.
[http://dx.doi.org/10.1016/j.jconrel.2021.04.005] [PMID: 33845057]
[24]
Pan, X.; Zhang, X.; Sun, H.; Zhang, J.; Yan, M.; Zhang, H. Autophagy inhibition promotes 5-fluorouraci-induced apoptosis by stimulating ROS formation in human non-small cell lung cancer A549 cells. PLoS One, 2013, 8(2), e56679.
[http://dx.doi.org/10.1371/journal.pone.0056679] [PMID: 23441212]
[25]
Dash, V.; Mishra, S.K.; Singh, M.; Goyal, A.K.; Rath, G. Release kinetic studies of aspirin microcapsules from ethyl cellulose, cellulose acetate phthalate and their mixtures by emulsion solvent evaporation method. Sci. Pharm., 2010, 78(1), 93-101.
[http://dx.doi.org/10.3797/scipharm.0908-09] [PMID: 21179372]
[26]
Kumar, G.; Gupta, R.; Sharan, S.; Roy, P.; Pandey, D.M. Anticancer activity of plant leaves extract collected from a tribal region of India. 3 Biotech, 2019, 2019, 9(11), 399.
[http://dx.doi.org/10.1007/s13205-019-1927-x] [PMID: 31656737]
[27]
Mohiyuddin, S.; Naqvi, S.; Packirisamy, G. Enhanced antineoplastic/therapeutic efficacy using 5-fluorouracil-loaded calcium phosphate nanoparticles. Beilstein J. Nanotechnol., 2018, 9(1), 2499-2515.
[http://dx.doi.org/10.3762/bjnano.9.233] [PMID: 30345213]
[28]
Kumar, S.U.; Matai, I.; Dubey, P.; Bhushan, B.; Sachdev, A.; Gopinath, P. Differentially cross-linkable core–shell nanofibers for tunable delivery of anticancer drugs: synthesis, characterization and their anticancer efficacy. RSC Advances, 2014, 4(72), 38263-38272.
[http://dx.doi.org/10.1039/C4RA05001K]
[29]
Lewandowska, M.A.; Jóźwicki, W.; Jochymski, C.; Kowalewski, J. Application of PCR methods to evaluate EGFR, KRAS and BRAF mutations in a small number of tumor cells in cytological material from lung cancer patients. Oncol. Rep., 2013, 30(3), 1045-1052.
[http://dx.doi.org/10.3892/or.2013.2579] [PMID: 23817662]
[30]
Safwat, M.A.; Soliman, G.M.; Sayed, D.; Attia, M.A. Gold nanoparticles enhance 5-fluorouracil anticancer efficacy against colorectal cancer cells. Int. J. Pharm., 2016, 513(1-2), 648-658.
[http://dx.doi.org/10.1016/j.ijpharm.2016.09.076] [PMID: 27693737]
[31]
Kim, D.; Jeong, Y.Y.; Jon, S. A drug-loaded aptamer-gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer. ACS Nano, 2010, 4(7), 3689-3696.
[http://dx.doi.org/10.1021/nn901877h] [PMID: 20550178]
[32]
Sun, S.B.; Liu, P.; Shao, F.M.; Miao, Q.L. Formulation and evaluation of PLGA nanoparticles loaded capecitabine for prostate cancer. Int. J. Clin. Exp. Med., 2015, 8(10), 19670-19681.
[PMID: 26770631]
[33]
Matai, I.; Sachdev, A.; Gopinath, P. Multicomponent 5-fluorouracil loaded PAMAM stabilized-silver nanocomposites synergistically induce apoptosis in human cancer cells. Biomater. Sci., 2015, 3(3), 457-468.
[http://dx.doi.org/10.1039/C4BM00360H] [PMID: 26222289]
[34]
Bhattacharjee, S. DLS and zeta potential - What they are and what they are not? J. Control. Release, 2016, 235, 337-351.
[http://dx.doi.org/10.1016/j.jconrel.2016.06.017] [PMID: 27297779]
[35]
Newton, D.W.; Kluza, R.B. pKa values of medicinal compounds in pharmacy practice. Drug Intell. Clin. Pharm., 1978, 12(9), 546-554.
[http://dx.doi.org/10.1177/106002807801200906]
[36]
Arias, J.L. Novel strategies to improve the anticancer action of 5-fluorouracil by using drug delivery systems. Molecules, 2008, 13(10), 2340-2369.
[http://dx.doi.org/10.3390/molecules13102340] [PMID: 18830159]
[37]
Ortiz, R.; Prados, J.; Melguizo, C.; Arias, J.L.; Ruiz, M.A.; Álvarez, P.J.; Caba, O.; Luque, R.; Segura, A.; Aránega, A. 5-Fluorouracil-loaded poly(ε-caprolactone) nanoparticles combined with phage E gene therapy as a new strategy against colon cancer. Int. J. Nanomedicine, 2012, 7, 95-107.
[http://dx.doi.org/10.2147/IJN.S26401] [PMID: 22275826]
[38]
Safwat, M.A.; Soliman, G.M.; Sayed, D.; Attia, M.A. Gold nanoparticles capped with benzalkonium chloride and poly (ethylene imine) for enhanced loading and skin permeability of 5-fluorouracil. Drug Dev. Ind. Pharm., 2017, 43(11), 1780-1791.
[http://dx.doi.org/10.1080/03639045.2017.1339082] [PMID: 28581826]
[39]
Gerweck, L.E.; Vijayappa, S.; Kozin, S. Tumor pH controls the in vivo efficacy of weak acid and base chemotherapeutics. Mol. Cancer Ther., 2006, 5(5), 1275-1279.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0024] [PMID: 16731760]
[40]
Sylvestre, J.P.; Kabashin, A.V.; Sacher, E.; Meunier, M.; Luong, J.H. Nanoparticle size reduction during laser ablation in aqueous solutions of cyclodextrins. Photon Proc. Microelectron. Photon., 2004, 5339, 84-92.
[http://dx.doi.org/10.1117/12.525499]
[41]
Jain, N.; Bhargava, A.; Panwar, J. Enhanced photocatalytic degradation of methylene blue using biologically synthesized “protein-capped” ZnO nanoparticles. Chem. Eng. J., 2014, 243, 549-555.
[http://dx.doi.org/10.1016/j.cej.2013.11.085]
[42]
Giteau, A.; Venier-Julienne, M.C.; Aubert-Pouëssel, A.; Benoit, J.P. How to achieve sustained and complete protein release from PLGA-based microparticles? Int. J. Pharm., 2008, 350(1-2), 14-26.
[http://dx.doi.org/10.1016/j.ijpharm.2007.11.012] [PMID: 18162341]
[43]
Asadi, N.; Annabi, N.; Mostafavi, E.; Anzabi, M.; Khalilov, R.; Saghfi, S.; Mehrizadeh, M.; Akbarzadeh, A. Synthesis, characterization and in vitro evaluation of magnetic nanoparticles modified with PCL–PEG–PCL for controlled delivery of 5FU. Artif. Cells Nanomed. Biotechnol., 2018, 46(sup1), 938-945.
[http://dx.doi.org/10.1080/21691401.2018.1439839] [PMID: 29468888]
[44]
Hirsch, L.R.; Stafford, R.J.; Bankson, J.A.; Sershen, S.R.; Rivera, B.; Price, R.E.; Hazle, J.D.; Halas, N.J.; West, J.L. Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc. Natlional Acad. Sci., 2003, 13549-13554.
[http://dx.doi.org/10.1073/pnas.2232479100]
[45]
Jaromi, L.; Csongei, V.; Vesel, M.; Abdelwahab, E.M.M.; Soltani, A.; Torok, Z.; Smuk, G.; Sarosi, V.; Pongracz, J.E. KRAS and EGFR mutations differentially alter ABC drug transporter expression in cisplatin-resistant non-small cell lung cancer. Int. J. Mol. Sci., 2021, 22(10), 5384.
[http://dx.doi.org/10.3390/ijms22105384] [PMID: 34065402]
[46]
Langer, C.J. Roles of EGFR and KRAS mutations in the treatment of patients with non–small-cell lung cancer. P&T, 2011, 36(5), 263-279.
[PMID: 21785539 ]

Rights & Permissions Print Cite
Article Metrics
16
1
© 2024 Bentham Science Publishers | Privacy Policy